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Cell adhesion and tissue factor upregulation in oxygenators used during coronary artery bypass grafting are modified by the Corline Heparin Surface
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
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2002 (English)In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, Vol. 36, no 6, 351-357 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Cardiopulmonary bypass (CPB) is associated with inflammatory response and activation of coagulation. We investigated the influence of a new heparin surface on the activation of cells retrieved from oxygenators used during coronary artery bypass grafting (CABG).

DESIGN: Sixty patients undergoing CABG with CPB were randomly assigned to either uncoated or completely Corline Heparin Surface (CHS)-coated circuits with one of three different levels of systemic heparin: standard, high or low. At end of surgery adhered cells were retrieved from the oxygenators and cell count, tissue factor (TF)- and CD11b-expression on monocytes and monocytic TFmRNA were analysed.

RESULTS: The heparin coating of the oxygenator prevented adhesion of granulocytes, monocytes and platelets. TF-expression on monocytes from the oxygenators was significantly higher than on circulating cells in all groups. Monocytes from the uncoated oxygenators showed low levels of TF-expression with high levels of TFmRNA. The coated group with high level of heparin showed higher surface-expression of TF with low levels of TFmRNA.

CONCLUSION: The CHS was most biocompatible with the standard level of heparin used during CABG whereas elevation of systemic heparin rather increased the activation and TF upregulation in monocytes from oxygenators.

Place, publisher, year, edition, pages
2002. Vol. 36, no 6, 351-357 p.
Keyword [en]
Tissue Factor, Cabg, Heparin, Leukocyte
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-91004DOI: 10.1080/140174302762659076PubMedID: 12626202OAI: oai:DiVA.org:uu-91004DiVA: diva2:163566
Available from: 2003-10-30 Created: 2003-10-30 Last updated: 2010-11-09Bibliographically approved
In thesis
1. Monocytes, Tissue Factor and Heparin-coated Surfaces: Clinical and Experimental Studies
Open this publication in new window or tab >>Monocytes, Tissue Factor and Heparin-coated Surfaces: Clinical and Experimental Studies
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cardiopulmonary bypass (CPB) is associated with inflammatory response and activation of coagulation. Heparin coating of the CPB circuit is shown to improve the biocompatibility of the surface. The biological effects of a new heparin surface, the Corline Heparin Surface (CHS), prepared according to a new principle, have been studied.

The CHS used during coronary artery bypass grafting with CPB in sixty patients prevented adhesion of cells to the extracorporeal device. The activation of inflammation, coagulation, and fibrinolysis was significantly reduced by the use of CHS. Both a reduced and an increased dose of systemic heparin in combination with the heparin-coated surface resulted in more activation of inflammation and coagulation.

Photoelectron spectroscopy studies of the molecular structure of the CHS demonstrated that a single layer of the heparin surface, equivalent to what was used in the in vivo studies, did not completely cover the substrate surface. Additional layer of immobilized heparin has resulted in a complete coverage. We examined the biological effects, i.e. activation of inflammation and coagulation, by CHS in one and two layers in an in vitro-study. The data from this study clearly demonstrated that a uniform surface coating of the CHS results in only minor activation of coagulation, inflammation and cell activation.

Monocytes do not normally express tissue factor (TF), initiator of the coagulation in vivo, but can be induced upon adhesion to artificial surfaces. TF is receptor for coagulation factor VIIa (FVIIa) and binding subsequently leads to formation of thrombin. Other biological effects beyond coagulation, as inflammation and angiogenesis, has recently been associated with the formation of TF·FVIIa. The TF∙FVIIa signal transduction induced an increased sensitivity to PDGF-BB-stimulated migration and an increased production of IL-8 and TNF-α in monocytes. These could be important mechanisms for continued recruitment of cells to sites of inflammation.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 65 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1299
Keyword
Medicine, monocytes, tissue factor, heparin-coated surfaces, coagulation, inflammation, thrombin, cytokines, cardiopulmonary bypass, biocompatibility, migration, chemotaxis, Medicin
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:uu:diva-3740 (URN)91-554-5779-7 (ISBN)
Public defence
2003-11-21, Robergsalen, ingång 40, Akademiska sjukhuset, Uppsala, 13:15
Opponent
Supervisors
Available from: 2003-10-30 Created: 2003-10-30Bibliographically approved

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Johnell, MatildaElgue, GracielaThelin, StefanLarsson, RolfSiegbahn, Agneta

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